This study has two specific aims: 1) to use longitudinal, objective techniques to characterize the clinical manifestations of early-onset bipolar disorder (BPD); and 2) to identify neurophysiological and neuropsychological correlates of affective dysregulation in bipolar children and adolescents. A particular focus of aim #2 is the identification of behavioral paradigms that assess psychological processes that are important in the pathophysiology of BPD, and that can be used either in subsequent fMRI studies (to identify dysfunctional neural circuitry in patients) or in family studies (to identify behavioral and biological markers of the illness i.e. endophenotypes). Approximately 50 patients and matched controls have been assessed on a battery of such paradigms. Taken together, these data indicate that children with BPD have difficulty adapting their behavior in response to changes in emotional stimuli in their environment. These deficits are evident on response reversal tasks, a task testing their ability to inhibit a dominant motor response and initiate another, and a task that assesses their behavior in the context of frustration. In addition, our data indicate that children with BPD have difficulty identifying facial emotion accurately. We hypothesize that these deficits are due to dysfunction in prefrontal-striatal-amygdala circuitry and, using fMRI, we have obtained some neuroimaging data to support that hypothesis. Based on these findings, we are initiating a study of adults with BPD and their children, who are at risk for the illness. The goal of that study is to ascertain whether the behavioral deifcits that we identified are familial and therefore may be candidate endophenotypes for BPD. In addition, this year we began recruiting children with ADHD as a psychiatric comparison group for children with BPD. Finally, we continue to assess the psychiatric status of family members, bank genetic samples from patients and parents for use in future studies, and follow the patients longitudinally (clinically and with structural MRI scans) for 4 years.